Urinary cell cycle arrest biomarker [TIMP-2]·[IGFBP7] in patients with hepatorenal syndrome

Biomarkers. 2019 Nov;24(7):692-699. doi: 10.1080/1354750X.2019.1652347. Epub 2019 Aug 22.

Abstract

Background: Patients with hepatorenal syndrome carry a high short-term mortality. Early diagnosis and treatment are essential for patients' outcome. Nevertheless diagnosis of HRS remains difficult. First-line therapy terlipressin is often associated with severe complications. Biomarkers become more on focus for an early diagnosis. Objective: The aim of this study was to test the diagnostic accuracy of urinary [TIMP-2]·[IGFBP7] for HRS patients and prognostic value for therapy responding patients. Material and methods: NephroCheck® measures urinary concentrations of TIMP-2 and IGFBP-7, both indicating stress of renal cells and associated with induction of cell cycle arrest. 22 HRS patients and 30 patients with normal kidney function were included. [TIMP-2]·[IGFBP7] was measured using NephroCheck®. HRS patients receiving terlipressin were also examined. Results: [TIMP-2]·[IGFBP7] values did not differ significantly (1.3 ± 2.09 vs. 1.03 ± 1.03; p = 0.55). Furthermore, there was no significant difference of [TIMP-2]·[IGFBP7] regarding response of terlipressin (1.32 ± 2.39 vs. 0.81 ± 1.05; p = 0.56). Low [TIMP-2]·[IGFBP7] values were significantly associated with higher mortality (p = 0.01). Conclusions: The results of this study suggest that [TIMP-2]·[IGFBP7] is not suitable for diagnostic of HRS and prediction of therapy response, but there might be evidence for prognostic value of [TIMP-2]·[IGFBP7] in regard to mortality of liver cirrhosis patients.

Keywords: Liver transplantation; [TIMP-2]·[IGFBP7]; acute kidney injury; biomarker; hepatorenal syndrome; terlipressin.

MeSH terms

  • Biomarkers / urine
  • Cell Cycle Checkpoints*
  • Early Diagnosis
  • Female
  • Hepatorenal Syndrome / diagnosis*
  • Hepatorenal Syndrome / mortality*
  • Hepatorenal Syndrome / pathology
  • Hepatorenal Syndrome / urine
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / urine*
  • Male
  • Middle Aged
  • Prognosis
  • Tissue Inhibitor of Metalloproteinase-2 / urine*

Substances

  • Biomarkers
  • Insulin-Like Growth Factor Binding Proteins
  • TIMP2 protein, human
  • insulin-like growth factor binding protein-related protein 1
  • Tissue Inhibitor of Metalloproteinase-2